The work of the molecular biology unit has focused on the identification of genetic alterations that contribute to the initiation and progression of malignant tumors in the central nervous system. A multifaceted approach has been taken to help determine the genetic alterations responsible for the expression of a malignant phenotype in CNS tumors. Studies of the expression of growth factors and growth factor receptors in glial tumors showed elevated expression of basic fibroblast growth factor (BFGF) and the BFGF high affinity receptor and increased levels of epidermal growth factor and alpha-platelet derived growth factor. Matrix metalloproteins and metalloproteases (MMPs) are postulated to be involved in the regulation of tumor invasiveness. Cellular invasiveness can be modulated by altering the balance between activated MMPs and their inhibitors. A new project to investigate the role of type IV collagen and collagenases, located in the basement membrane, in determining invasive activity in pituitary tumors has been initiated. Analyses of genetic alterations demonstrated a loss of heterozygosity on chromosomes 10 and 17 in a significant percent of glial tumors. Although the p53 gene locus lies on chromosome 17, deletions in this gene were rare, implying that a second, as yet unidentified, tumor suppressor gene is located on the short arm of chromosome 17, distal to the p53 locus, and that inactivation of the second tumor suppressor gene may function in the initiation or progression of astrocytic neoplasms. In Nelson's tumors loss of heterozygosity of chromosome 17 and point mutation in p53 were identified in two of six tumors. Metastatic lesions from primary non CNS tumors and recurrent tumors exhibited alterations in p53 suggesting that loss of wild-type p53 contributes to tumor progression and spread. The cyclin-dependent kinase 4 inhibitor gene, p16, on chromosome 9, has been implicated in progression of malignancy in tumors. A study of deletion of the p16 gene was undertaken in DNA extracted from glioblastoma multiform (GBM) tissue. Homozygous deletion of p16 was common in primary GBM. Comparisons between primary and recurrent tumors show that a higher percentage of recurrent GBM show deletion on p16 which extend toward the telomere and the centromere.